You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
Expected results<br />
• Establishment of a large database including sequences<br />
of idiotypic VH and VL genes expressed by a variety<br />
of lympho-proliferative disorders, including low grade<br />
B-NHL, autoimmunity-associated lympho-proliferations,<br />
and chronic lymphocytic leukemia. This will allow the<br />
identifi cation of candidate Id proteins for ‘cross-reactive’<br />
immunotherapy.<br />
• Pre-clinical characterisation of the immunogenicity of<br />
selected natural Id proteins, with particular regard<br />
to their ability to induce immune responses against<br />
lymphoma cells expressing molecularly correlated Id<br />
proteins. The characterisation will include the identification<br />
of B cell epitopes and HLA Class I-restricted<br />
cytotoxic T cell epitopes using innovative approaches<br />
and will allow the development of dedicated assays for<br />
immunomonitoring.<br />
• Design and validation of optimised Id vaccines.<br />
• Evaluation and validation of new adjuvants and innovative<br />
delivery systems for improved Id vaccine formulations<br />
and administration.<br />
• ‘Clinical-grade’ production and purifi cation of optimised<br />
Id proteins for patient vaccination.<br />
The SMEs are an integral part in the project in making the<br />
new diagnostic and therapeutic tools available, not only for<br />
Europe but also for the world market. The close integration<br />
between clinical and research activities at several university<br />
hospitals and cancer centres with the SMEs will form new<br />
centres of excellence where European SMEs will benefi t<br />
from close collaboration, at the same time as new diagnostic<br />
and therapeutic products will be developed to the<br />
benefi t of patients with lymphoid malignancies.<br />
Potential applications<br />
The results obtained in the present project will allow the<br />
design and activation of phase I/II clinical trials aimed at<br />
validating the use of optimised, pre-made vaccines for the<br />
treatment of a relatively broad spectrum of lymphoid malignancies.<br />
The proposed Id vaccination may be benefi cial also<br />
for patients with pre-neoplastic B-cell lymphoproliferations,<br />
such as mixed cryoglobulinaemia. These vaccines, in fact,<br />
may be used with the purpose of alleviating symptoms and,<br />
ultimately, preventing a possible evolution towards an overt<br />
B cell malignancy. Once validated as drugs, the vaccines will<br />
have the advantage of being easily distributed to all hematology<br />
and oncology departments, including those of<br />
peripheral hospitals/universities. Thus, results obtained in<br />
the present project will have an important strategic impact<br />
in solving, at least in part, the dramatic social and health<br />
problem represented by NHL.<br />
228<br />
Flow chart, outlining the main expected results, leading from identifi cation of shared idiotypes<br />
to the development of optimized vaccines for the treatment of B-cell lymphoproliferations.<br />
CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME